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Drug resistance in colon cancer

R Gorlick1, J R Bertino

  • 1Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

Seminars in Oncology
|December 22, 1999
PubMed

Insights

Drug resistance in colorectal cancer management is a major challenge. Understanding resistance mechanisms to chemotherapy, like fluoropyrimidines, is key to developing new treatments.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Intrinsic and acquired drug resistance significantly impede colorectal cancer treatment success.
  • Mechanisms of resistance involve altered drug transport, metabolism, target modification, cell cycle regulation, and DNA repair pathways.

Purpose of the Study:

  • To review the mechanisms of action and resistance for fluoropyrimidines and raltitrexed in colorectal cancer.
  • To highlight recent studies utilizing patient-derived tumor samples to elucidate these resistance mechanisms.

Main Methods:

  • Review of existing literature on fluoropyrimidine and raltitrexed mechanisms.
  • Analysis of studies focusing on colorectal and gastric tumor samples from patients.
  • Examination of genetic alterations related to drug resistance.

Main Results:

  • Drug resistance in colorectal cancer is multifactorial, involving cellular and molecular changes.
  • Specific alterations in drug influx, efflux, metabolism, target, cell cycle, and DNA repair contribute to resistance.
  • Recent research provides insights into these mechanisms using clinical tumor samples.

Conclusions:

  • A comprehensive understanding of drug resistance mechanisms is crucial for improving colorectal cancer therapy.
  • Future clinical trials are expected to leverage this knowledge for more effective treatment strategies.
  • Targeting specific resistance pathways may overcome chemotherapy failure in colorectal cancer patients.

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